Large Hepatocellular Carcinoma Patients Research Articles

Comparative study on the efficacy and safety of transarterial chemoembolization combined with hepatic arterial infusion chemotherapy for large unresectable hepatocellular carcinoma.

Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) are two new treatments for hepatocellular carcinoma (HCC). Previous studies had reported that TACE combined with HAIC conferred better survival benefit than TACE alone. The study was to evaluate the availability and safety of TACE combined with HAIC for the treatment of large HCC. Patients with unresectable large HCC who underwent TACE combined with HAIC (TACE-HAIC group) and HAIC alone (HAIC group) at the Department of Interventional Radiology between August 2018 and September 2022 were retrospectively enrolled in this study. Overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs) were used to evaluate the efficacy and safety of the two groups by using log-rank test. The independent factors of OS of large HCC patients were investigated by Cox regression model. A total of 73 patients (mean age, 59.8±8.8; 60 men) with unresectable large HCC were finally screened in the current study, including 32 who received TACE combined with HAIC and 41 who received HAIC alone. Compared with patients in HAIC group, TACE-HAIC group had higher median OS (37.1 vs. 14.9 months, P=0.0014). Similarly, PFS in the TACE-HAIC group was longer than that in the HAIC group (16.5 vs. 6.9 months, P=0.0037). The objective response rate (ORR) was 65.6% vs. 53.7% and the disease control rate (DCR) was 90.6% vs. 78.0% in the two groups, neither was statistically significant (P=0.345 and 0.208, respectively). All AEs related to therapy were manageable, and there were no significant differences in the incidence of any grade and grade 3/4 AEs between the two groups (P>0.05). TACE combined with HAIC yielded a promising prognosis in treating patients with large HCC compared with HAIC alone, with tolerable toxicity.

Evaluation of the efficacy and safety of CalliSpheres® microsphere-transarterial chemoembolization in large hepatocellular carcinoma.

The prognosis of large hepatocellular carcinoma (HCC) is still unfavorable due to limited and challenging treatment. CalliSpheres® microsphere-transarterial chemoembolization (CSM-TACE) is an effective therapy for general HCC but not frequently applied for large HCC. Hence, this study aimed to investigate the efficacy and safety of CSM-TACE in large HCC patients. This prospective study analyzed 100 large HCC (tumor size >5 cm) patients receiving CSM-TACE. Treatment response, survival, change in liver function indexes, and adverse events were recorded. The best complete response, partial response, stable disease, and progressive disease rates were 2.0%, 31.3%, 65.7%, and 1.0%, respectively, leading to the best objective response rate (ORR) of 33.3% and disease control rate of 99.9%. Multivariate analysis showed that intrahepatic metastasis was independently related to poor ORR (odd ratio = 0.366, P = 0.023). The 1- and 2-year progression-free survival (PFS) rates were 88.9% and 80.6%, with a mean [95% confidence interval (CI)] PFS of 21.6 (20.4-22.9) months. The 1- and 2-year overall survival (OS) rates were 99.0% and 99.0%, with a mean (95% CI) OS of 23.8 (23.3-24.2) months. Total bilirubin (P < 0.001), alanine transaminase (P < 0.001), aspartate transaminase (P < 0.001), and α-fetoprotein (P = 0.045) were abnormal in a short-term period then stably recovered from 1 month ± 15 days after drug-eluting bead-TACE to 24 months ± 15 days. During hospitalization and postdischarge, tolerable abdominal pain and decreased appetite were common adverse events. CSM-TACE shows favorable treatment response and survival with acceptable tolerance among large HCC patients, indicating that it may promote the management of these patients.

Perioperative and long-term survival outcomes of laparoscopic versus open hepatectomy for BCLC stage A large hepatocellular carcinoma patients in difficult segments: A two-centre, propensity score matching analysis.

The differences in short- and long-term outcome between laparoscopic liver resection (LLR) and open liver resection (OLR) for BCLC stage A large hepatocellular carcinoma (HCC) in difficult segments (I, IVa, VII, VIII) remain unclear. This PSM two-centre study aimed to compare perioperative and long-term survival outcomes of LLR with OLR for this HCC. HCC patients with BCLC stage A who underwent OLR or LLR in two medical centres were enrolled in the study. PSM analysis was performed to match patients between the LLR cohort and OLR cohort. Survival was analysed based on the Kaplan-Meier method. Independent risk factors were identified by Cox regression. After PSM, 35 patients remained in the LLR cohort, and 84 remained in the OLR cohort. Patients in the LLR cohort had more intraoperative blood loss (p=0.036) and shorter hospital stays after surgery (p<0.001). The LLR cohort and OLR cohort had no difference in intraoperative blood transfusion, surgical margin or postoperative short-term outcomes. The OS and RFS were not significantly different between the two cohorts. The OS and RFS of these two cohorts were not different in the subgroup analysis. Surgical margin was identified as an independent risk factor for tumour recurrence. For BCLC stage A large HCC patients with lesions in difficult segments, LLR was feasible and had shorter hospital stay than OLR. In addition, a surgical margin ≥1 cm could significantly decrease the recurrence probability for large HCC located in different segments without compromising short-term outcomes.

Clinical prognosis of surgical resection versus transarterial chemoembolization for single large hepatocellular carcinoma (≥5cm): A propensity score matching analysis.

Favorable prognostic factors and therapeutic strategies are important for patients with single large hepatocellular carcinoma (HCC). This retrospective study aimed to investigate the prognostic factors in patients with single large (≥5cm) HCC with Child-Pugh (CP) class A patients and to recommend therapeutic strategies. Overall, 298 HCC patients with single and large (≥5cm) tumors with CP class A, but without distant metastasis and macrovascular invasion were included, and their clinicopathological data, overall survival (OS), and progression-free survival (PFS) were recorded. OS and PFS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed. The 298 HCC patients were 79.2% male and median age of 64 years. For the initial treatment, surgical resection (SR) and transarterial chemoembolization (TACE) was 50.8% and 49.2%, respectively. The OS and PFS were significantly higher in patients receiving SR than those receiving TACE before and after PSM. Furthermore, in multivariate analysis, cirrhosis (Hazard ratio [HR]: 2.04; 95% confidence interval [CI]: 1.35-3.03, p < 0.001, CP class A5/6 [HR: 4.01; 95% CI: 2.43-6.66, p < 0.001], and initial treatment [SR vs. TACE HR=3.23; 95% CI: 2.13-5.01, p < 0.001]) remained significantly associated with mortality. Moreover, in multivariate analysis, CP class A5/6 (HR: 3.23; 95% CI: 1.89-5.88, p < 0.001), and initial treatment (Resection vs. TACE; HR=4.17; 95% CI: 1.64-8.33, p=0.039) remained significantly associated with recurrence. In conclusion, SR was associated with significantly higher OS and PFS rates than TACE before and after PSM for single large HCC patients.

Development and validation of prognostic nomograms for large hepatocellular carcinoma after HAIC

Hepatic arterial infusion chemotherapy (HAIC) using the FOLFOX regimen (oxaliplatin plus fluorouracil and leucovorin) is a promising option for large hepatocellular carcinoma (HCC). However, post-HAIC prognosis can vary in different patients due to tumor heterogeneity. Herein, we established two nomogram models to assess the survival prognosis of patients after HAIC combination therapy. A total of 1082 HCC patients who underwent initial HAIC were enrolled between February 2014 and December 2021. We built two nomogram models for survival prediction: the preoperative nomogram (pre-HAICN) using preoperative clinical data and the postoperative nomogram (post-HAICN) based on pre-HAICN and combination therapy. The two nomogram models were internally validated in one hospital and externally validated in four hospitals. A multivariate Cox proportional hazards model was used to identify risk factors for overall survival (OS). The performance outcomes of all models were compared by area under the receiver operating characteristic curve (AUC) analysis with the DeLong test. Multivariable analysis identified larger tumor size, vascular invasion, metastasis, high albumin-bilirubin grade, and high alpha-fetoprotein as indicators for poor prognosis. With these variables, the pre-HAICN provided three risk strata for OS in the training cohort: low risk (5-year OS, 44.9%), middle risk (5-year OS, 20.6%), and high risk (5-year OS, 4.9%). The discrimination of the three strata was improved significantly in the post-HAICN, which included the above-mentioned factors and number of sessions, combination with immune checkpoint inhibitors, tyrosine kinase inhibitors, and local therapy (AUC, 0.802 versus 0.811, p < 0.001). The nomogram models are essential to identify patients with large HCC suitable for treatment with HAIC combination therapy and may potentially benefit personalized decision-making. Hepatic arterial infusion chemotherapy (HAIC) provides sustained higher concentrations of chemotherapy agents in large hepatocellular carcinoma (HCC) by hepatic intra-arterial, result in better objective response outperformed the intravenous administration. HAIC is significantly correlated with favorable survival outcome and obtains extensive support in the effective and safe treatment of intermediate advanced-stage HCC. In view of the high heterogeneity of HCC, there is no consensus regarding the optimal tool for risk stratification before HAIC alone or HAIC combined with tyrosine kinase inhibitors or immune checkpoint inhibitors treatment in HCC. In this large collaboration, we established two nomogram models to estimate the prognosis and evaluate the survival benefits with different HAIC combination therapy. It could help physicians in decision-making before HAIC and comprehensive treatment for large HCC patients in clinical practice and future trials.

Laparoscopic versus open hepatectomy for large hepatocellular carcinoma: a single center propensity-score-matching comparative analysis of perioperative outcomes and long-term survival.

Although the benefits of laparoscopic hepatectomy (LH) for hepatocellular carcinoma (HCC) in most circumstances are evident, the benefits for large HCC are contentious. This study aimed to compare the perioperative outcomes and survival after LH versus open hepatectomy (OH) in large HCC patients. An analysis of prospectively maintained database included 215 hepatectomies for large HCC (diameter ≥ 5cm). The operative and survival outcomes were compared between the LH group (n = 109) and the OH group (n = 106). Propensity score matching (PSM) 1:1 included 70 patients in each group. The entire cohort multivariable analyses were performed to identify the factors associated with surgical complications and suboptimal recurrence-free survival (RFS). After PSM, baseline characteristics and the extent of liver resection were similar in both groups. The LH group had a shorter hospital stay than the OH group (7 vs 9.5days, p = 0.001). The R0 resection rate, complication rate, overall survival, and RFS were similar between the groups. The multivariate analyses revealed two independent factors predicting surgical complication (major resection; p < 0.001 and large volume blood loss; p = 0.042), and 3 independent factors predicting suboptimal RFS including R1 resection (p = 0.011), multifocal HCC (p = 0.005), and microvascular invasion (p = 0.001). LH was not associated with surgical complication and suboptimal RFS. Our study highlights the benefits of LH by improving the perioperative outcomes, without long-term survival inferiority in selected large HCC patients compared with conventional OH. LH can be an attractive option for large HCC treatment.

Transarterial chemoembolization combined with radiofrequency ablation in the treatment of large hepatocellular carcinoma with stage C.

The combination therapy of transarterial chemoembolization and radiofrequency ablation (TACE-RFA) shows promising efficacy in large hepatocellular carcinoma (HCC). Data on the clinical efficacy and safety of TACE-RFA for large HCC with barcelona clinic liver cancer (BCLC) stage C are lacking in China. To determine the safety and efficacy of TACE-RFA for large, advanced HCC. Patients of HCC with BCLC stage C who were treated with TACE-RFA or TACE alone at our institute from August 2008 to January 2017 were retrospectively reviewed. The complications were observed. The associations between overall survival (OS) and treatment method were analysed. Data were collected from 102 HCC patients. Among them, 64 underwent TACE-RFA and 38 underwent TACE. The combination of TACE and RFA was safe. All complications were controllable. The median OS in the TACE-RFA group was significantly longer than that in the TACE group (8.0 mo vs 4.0 mo, P = 0.000). The 6-, 12- and 24-mo survival rates of the combination group were 68.8%, 34.4%, and 10.9%, respectively, while those of the TACE group were 36.8%, 7.9%, and 0% (P < 0.05). TACE-RFA has an advantage over TACE alone in improving OS in large HCC patients with BCLC stage C.

Intended preoperative trans-arterial embolization for large hepatocellular carcinoma: a retrospective cohort study

BackgroundGenerally, a large tumor size of hepatocellular carcinoma (HCC) is associated with poor visibility and uncertainty in the surgical field which results in increased surgical difficulty as well as unfavorable postoperative outcomes. We performed intended preoperative trans-arterial embolization (TAE) in patients with a large HCC. In this study, we investigated the oncological significance of intended preoperative TAE for a large HCC, using a comparison between patients with and without TAE, and detailed analyses for pre- and post-TAE status.MethodsA total of 411 patients who underwent hepatectomy for primary HCC at the University of Yamanashi Hospital between January 2007 and December 2018 were included in this study. The patients were divided into two groups: patients with larger HCCs (≥50 mm, n=51) and those with smaller HCC (<50 mm, n=360) according to the size of their HCCs. Comparison of clinicopathological features between these groups and clinical outcomes between the TAE and non-TAE groups were compared. In addition, a detailed analysis of each case in the TAE group was conducted, comparing clinicopathological factors between pre- and post-TAE status.ResultsThe clinical unfavorable short- and long-term outcomes of patients with large HCCs (≥50 mm) were revealed compared to those with small HCCs (<50 mm). The prognostic analyses showed that a large tumor size and increased tumor markers, multiple tumor numbers, and others were adverse prognostic factors, and vascular invasions and residual tumors were included in the multivariate analysis.Further detailed analyses revealed that the average rates of change in tumor size and tumor shrinkage after TAE were − 48.6±35.6 mm and − 30.7±17.0%, respectively. Pathological high necrotic changes in the tumor, after multiple-times TAE aiming to a better effect, were related to a better prognosis in patients with large HCC. Poor prognostic factors became less common in patients who underwent intended preoperative TAE, and these patients had better prognoses.ConclusionsThe large tumor size of HCC is associated with unfavorable outcomes; the intended preoperative TAE for large HCC patients performed multiple times aiming to affect the tumor as much as possible might improve their prognoses.

Impact of Tumor Size on Outcome of Hepatectomy for Hepatocellular Carcinoma: A Nationwide Propensity Score Adjusted Analysis

Introduction: Surgical outcomes of large hepatocellular carcinoma (HCC) have not yet been fully evaluated. The aim of this study was to compare the surgical outcomes after liver resection for HCC according to tumor using a large, nationwide cancer registry-based cohort and propensity score matching. Method: From 2008 to 2015, a total of 12,139 patients were diagnosed with liver cancer and registered in the Korean Primary Liver Cancer Registry (KPLCR). Of those, patients who underwent hepatectomy as primary treatment without distant metastasis were selected. We performed 1:1 propensity score matching between the small group (<5cm) vs. medium group (≥5cm and <10cm) and medium group vs. large group (≥10cm) each. Results: Overall, 265 patients each in the small group and medium group were compared while 64 patients each in the medium group and the large group were compared. The proportion of microvascular invasion was higher in the medium group compared to the small group. Overall survival rate and progression-free survival rate was lower in the medium group compared to the small group. There was a tendency of poorer overall survival in the large group compared to the medium group. Progression-free survival rate was significantly lower in the large group compared to the medium group. Conclusions: Although primary liver resection can be considered even in large HCC patients, greater caution with careful screening for recurrence is needed.

Efficacy of liver resection for single large hepatocellular carcinoma in Child-Pugh A cirrhosis: Analysis of nationwide cancer registry database

Therapeutic strategies are still debated and further studies are needed on prognostic factors for patients with single large hepatocellular carcinoma (HCC). This study aimed to identify the prognostic factors of single large HCC patients with good performance status and Child-Pugh A cirrhosis using large national cancer registry database and recommend therapeutic strategy in patients with such condition. Among 12,139 HCC patients registered at the Korean Primary Liver Cancer Registry (KPLCR) from 2008 through 2015, single large (≥ 5 cm) HCC patients with Eastern Cooperative Oncology Group (ECOG) performance status 0 and Child-Pugh score A were selected. 466 patients were analyzed. The 1-, 2-, 3-, and 5-year survival rates after initial treatment were 84.9%, 71.0%, 60.1%, and 51.6%, respectively and the 1-, 2-, 3-, and 5-year progression-free survival rates were 43.6%, 33.0%, 29.0%, and 26.8%, respectively. While platelet count < 100 × 109/L (p < 0.001), sodium level < 135 mmol/L (p = 0.002), maximum tumor diameter ≥ 10 cm (p = 0.001), and treatment other than resection (transarterial therapy vs. resection: p < 0.001, others vs. resection: p = 0.002) were significantly related to poorer overall survival, sodium < 135 mmol/L (p = 0.015), maximum tumor diameter ≥ 10 cm (p < 0.001), and treatment other than resection (transarterial therapy vs. resection: p < 0.001, others vs. resection: p = 0.001) were independently related with poorer progression-free survival. Resection as initial treatment should be considered when possible even in single large HCC patient with good performance and mild cirrhosis. Physicians should pay more attention to patients with low platelet level (< 100 × 109/L), serum sodium level (< 135 mmol/L), and maximum tumor diameter ≥ 10 cm.

Identification of Clinical Phenotypes and Related Survival in Patients with Large HCCs.

Simple SummaryFactors influencing the survival of hepatocellular carcinoma (HCC) patients include portal vein thrombosis (PVT), tumor numbers (multifocality), blood alpha-fetoprotein (AFP) levels, and the degree of liver damage (levels of blood bilirubin and albumin). However, the role of tumor size can be ambiguous. We therefore examined multiple clinical characteristics for their relationship with patient death and combined the three parameters with the greatest impact to create a tool to examine the characteristics and survival of patients with normal and abnormal levels of this three-parameter tool. In patients with large tumors, we found that normal levels of these three parameters—no PVT or multifocality plus normal blood albumin levels—were associated with longer survival than any group containing patients with PVT. This good-survival group could also be divided into two subgroups, differing in survival, based on blood AFP levels. This three-parameter tool might be prognostically useful in stratifying patients and management decisions.Background. Hepatocellular carcinoma (HCC) factors, especially maximum tumor diameter (MTD), tumor multifocality, portal vein thrombosis (PVT), and serum alpha-fetoprotein (AFP), influence survival. Aim. To examine patterns of tumor factors in large HCC patients. Methods. A database of large HCC patients was examined. Results. A multiple Cox proportional hazard model on death identified low serum albumin levels and the presence of PVT and multifocality, with each having a hazard ratio ≥2.0. All combinations of these three parameters were examined in relation to survival. Using univariate Cox analysis, the combination of albumin >3.5 g/dL and the absence of both PVT and multifocality had the best survival rate, while all combinations that included the presence of PVT had poor survival and hazard ratios. We identified four clinical phenotypes, each with a distinct median survival: patients with or without PVT or multifocality plus serum albumin ≥3.5 (g/dL), with each subgroup displaying high (≥100 IU/mL) or low (<100 IU/mL) blood AFP levels. Across a range of MTDs, we identified only two significant trends, blood AFP and platelets. Conclusions. Patients with large HCCs have distinct phenotypes and survival, as identified by the combination of PVT, multifocality, and blood albumin levels.

Assessment of efficacy and safety by CalliSpheres versus HepaSpheres for drug-eluting bead transarterial chemoembolization in unresectable large hepatocellular carcinoma patients

This study aimed to compare efficacy and safety of HepaSpheres and CalliSpheres in unresectable large hepatocellular carcinoma (HCC) patients. One hundred and twenty-seven unresectable large HCC patients receiving drug-eluting bead transarterial chemoembolization (DEB-TACE) treatment with CalliSpheres or HepaSpheres microspheres were analyzed. Treatment response, Karnofsky performance status (KPS) score, adverse events, main liver function indexes, time to progression (TTP), and overall survival (OS) were analyzed. Objective response rate (82.7% vs. 63.8%, p=.030) and disease control rate (100.0% vs. 91.5%, p=.030) were increased in CalliSpheres group compared to HepaSpheres group at 1 month after treatment, while no difference was found between the two groups regarding treatment response at 3 or 6 months post treatment (all p>.05). The KPS score at 1, 3, and 6 months was similar between the two groups (all p>.05). As for the liver function, the ALT, AST, ALB, and TBIL levels at 7 and 30 days were of no difference between the two groups (all p>.05). In addition, the adverse events including nausea/vomiting, pain, fever, myelosuppression, biloma, and abscess were of no difference between the two groups, either (all p>.05). In terms of survival profile, there was no difference regarding TTP (6.3 months (95%CI: 5.9–6.6 months) vs. 6.0 months (95%CI: 5.6–6.4 months), p=.082) or OS (23.0 months (95%CI: 20.1–25.9 months) vs. 22.0 months (95%CI: 20.2–23.8 months), p=.571) between the two groups. In conclusion, CalliSpheres seems to be superior in short-term efficacy and equal in long-term efficacy as well as safety compared to HepaSpheres for DEB-TACE treatment in unresectable large HCC patients.

Comparison of Angio-CT and cone-beam CT-guided immediate radiofrequency ablation after transcatheter arterial chemoembolization for large hepatocellular carcinoma.

To evaluate the rapeutic effectiveness of Angio-CT or cone-beam CT (CBCT)-guided immediate radiofrequency ablation (RFA) after transcatheter arterial chemoembolization (TACE) for large hepatocellular carcinoma (HCC). 117 large HCC patients (mean maximum diameter: 9.3cm; range 5.3-17.7cm) were retrospective studied and divided into Angio-CT group (n = 66 cases), CBCT group (n = 21 cases), and single TACE group (n = 30 cases) according to treatment (Angio-CT/CBCT-guided immediate RFA after TACE, single TACE, respectively). The operative time, effective radiation dose, local-regional tumor responses, overall survival (OS), and progression‑free survival (PFS) time and complications were recorded. The operative time and effective radiation dose of Angio-CT group and CBCT group were higher than those of TACE group (P < 0.01). The local-regional tumor responses on 1-month follow-up MRI (complete response + partial response) of Angio-CT group and CBCT group were 100%, which were significantly higher than that of single TACE group (76.7%, P < 0.05). There was no significant difference in local-regional tumor responses of 1-month follow-up between Angio-CT group and CBCT group (P = 0.831). The median PFS and OS time of Angio-CT group were 14.7 ± 1.43months and 18.21 ± 0.88months, CBCT group were 13.9 ± 1.53months and 17.87 ± 1.78months, TACE group were 10.4 ± 1.21months and 12.87 ± 0.91months, respectively. No procedure-related major complications occurred. MIYABI Angio-CT or CBCT-guided immediate RFA after TACE for large HCC both have more effective than single TACE. The former is worth popularizing, due to its advantages of convenience, shorter operative time, and less radiation dose for doctors.

Laparoscopic Versus Open Left Lateral Segmentectomy for Large Hepatocellular Carcinoma: A Propensity Score-Matched Analysis.

With the advancement of endoscopic technology, laparoscopic liver resection has become the standard procedure for left lateral segmentectomy. The aim of this study was to compare perioperative and oncological outcomes between laparoscopic and open left lateral segmentectomy for hepatocellular carcinoma (HCC) >5 cm. A total of 66 patients underwent left lateral segmentectomy for HCC (>5 cm) during the period spanning between 2013 and 2015. To overcome selection bias, 1:3 match using propensity score-matched analysis was performed between laparoscopic and open liver resection. Relatively smaller tumor size (6.0 vs. 7.0 cm; P=0.030) and more frequent incidence of complete tumor capsule (93.3% vs. 58.8%; P=0.013) were observed in the laparoscopic group compared with the open group before matching. Although the longer operation time (195 vs. 150 min; P=0.022) was consumed in the laparoscopic procedure after matching, the laparoscopic group had shorter postoperative hospital stay (6 vs. 7 d; P=0.002) and less blood loss volume (50 vs. 100 mL; P=0.022). The Pringle maneuver for hepatic inflow occlusion was more likely to be applied in patients who underwent open surgery. The incidence of postoperative complication seemed to be lower in the laparoscopic group (6.7%) compared with that in the open group (11.8%) before matching. On the basis of propensity score-matched analysis, the complication rates were comparable between the 2 groups (7.1% vs. 6.7%, P=0.953). No difference in the 1-year and 3-year overall and recurrence-free survival rates was found between the laparoscopic and open groups. Laparoscopic left lateral segmentectomy for large HCC patients showed better perioperative outcomes and equivalent oncologic outcomes as the open procedure, providing evidence for considering as a standard laparoscopic practice through careful selection.

Serum albumin levels in relation to tumor parameters in hepatocellular carcinoma patients.

Serum albumin levels have been shown to have prognostic significance in hepatocellular carcinoma (HCC), as part of an inflammatory index. The aim of this study was to examine the possible relationship of serum albumin levels to parameters of HCC aggressiveness. A large HCC patient cohort was retrospectively examined, and the possible relationships of albumin levels to tumor diameter, multifocality, portal vein thrombosis (PVT) and α-fetoprotein levels were examined. HCC patients with lower serum albumin levels had significantly larger maximum tumor diameters, greater prevalence of PVT, increased tumor multifocality and higher α-fetoprotein levels, than HCC patients with higher albumin levels. A correlation was found between levels of these tumor parameters and serum albumin levels. These results indicate that low serum albumin levels correlate with increased parameter measures of HCC aggressiveness, in addition to their role as a monitor of systemic inflammation. Decreased serum albumin might have a role in HCC aggressiveness.

The effect of radiotherapy in liver-confined but non-resectable Barcelona Clinic Liver Cancer stage C large hepatocellular carcinoma.

Background and aimsClinical trials to determine the efficacy of radiotherapy (RT) in liver-confined but non-resectable Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) are scarce. We aimed to determine the benefit of RT in such tumors and investigated large HCC tumors.MethodsHCC data from the Korea Central Cancer Registry recorded from 2008 to 2010 were used. A total of 593 patients met our inclusion criteria; 67 were treated with RT while the remainder made up the non-RT group. Fifty-two RT recipients underwent combination treatments within 4 weeks after the first RT treatment, and were defined as the combination RT group. We performed propensity score matching (PSM) to compare the RT or combination RT groups with the non-RT group. The endpoint was overall survival (OS).ResultsMedian follow-up time for surviving patients was 48 months. After PSM, there was no difference in OS between the RT and non-RT groups or between the combination RT and non-RT groups. However, the combination RT group had a longer median survival time (MST) (10.7 vs. 6.9 months, respectively). Next, we conducted PSM between the combination RT and non-RT groups in patients with tumor sizes ≥10 cm; MST was significantly longer in the former group (10.1 vs. 5.4 months, respectively; bootstrap 95% confidence interval of the difference in MST: 0.2-11.8).ConclusionsAs a combined modality, RT is a plausible therapeutic option for liver-confined but non-resectable BCLC stage C large HCC patients.

A Hepatocellular Carcinoma Aggressiveness Index and Its Relationship to Liver Enzyme Levels

Background: Prognosis in hepatocellular carcinoma (HCC) is influenced by both liver and tumor factors, which have been considered independent influences. However, recent evidence has shown that the underlying liver also has prognostic information. Aims: To investigate possible relationships between liver function parameters and HCC aggressiveness indices. Methods: A large HCC patient database with baseline clinical information and survival data was retrospectively examined. Results: Data on 756 HCC patients with normal bilirubin were examined for a relationship between serum liver enzymes and 4 HCC aggressiveness indices of maximum tumor diameter, portal vein invasion, tumor multifocality or serum alpha-fetoprotein levels. An association was found between elevated enzyme levels and increased HCC aggressiveness. An aggressiveness index was constructed from the 4 indices and expressed as a sum of their scores, which in turn reflected 3 survival groups. In a Cox model, the hazard ratios for each of the groups were significantly different. Conclusions: Statistically significant correlations were found between standard liver function parameters and HCC aggressiveness. A composite aggressiveness index was constructed, yielding 3 groups with different survival probabilities. These findings support the concept of the importance of the underlying liver in relation to HCC biology.

Down-regulation of sirtuin 3 is associated with poor prognosis in hepatocellular carcinoma after resection.

BackgroundSirtuin 3 (Sirt3), one of the seven Sirtuins family members, plays critical roles in the progression of multiple cancer types. However, its role in the prognosis of hepatocellular carcinoma (HCC) has not yet been investigated systematically.MethodsThe correlation of Sirtuins expression with prognosis of HCC was determined by immunohistochemistry (IHC) in a large HCC patient cohort (n = 342). Expression of Sirt3 in tumoral and peritumoral tissues of HCC patients were further determined by western blotting (WB).ResultsIHC and WB studies both showed a decreased expression of Sirt3 in tumoral tissues compared with peritumoral tissues (P = 0.003 for IHC, P = 0.0042 for WB). Decreased expression of Sirt3 in both tumoral and peritumoral tissues was associated with increased recurrence probability and decreased overall survival rate by univariate analyses (intratumoral Sirt3: P = 0.011 for TTR, P = 0.001 for OS; peritumoral Sirt3: P = 0.017 for TTR, P = 0.023 for OS), the prognostic value was strengthened by multivariate analyses (intratumoral Sirt3: P = 0.031 for TTR, P = 0.001 for OS; peritumoral Sirt3: P = 0.047 for TTR, P = 0.031 for OS). Intratumoral Sirt3 also showed a favorable prognostic value in patients with BCLC stage A (TTR, P = 0.011; OS, P < 0.001). In addition, we found that IHC studies of other sirtuin members showed a decreased expression of Sirt2, Sirt4 and Sirt5 and an increased expression of Sirt1, Sirt6 and Sirt7 in intratumoral tissues compared with peritumoral tissues. In contrast to Sirt3, other members did not showed a remarkable correlation with HCC prognosis.ConclusionsDown-regulation of intratumoral and peritumoral Sirt3 were both associated with poor outcome in HCC, moreover, intratumoral Sirt3 was a favorable prognostic predictor in early stage patients.

Role of the 1-month protocol transarterial chemoinfusion in detecting intrahepatic metastasis after resection of large hepatocellular carcinoma greater than 10 cm.

Backgrounds/AimsTumor recurrence is very common after hepatic resection of hepatocellular carcinoma (HCC) ≥10 cm. The purpose of this study was to validate the prognostic significance of the preoperative alkaline phosphatase (ALP) level and early intrahepatic metastasis in HCC patients who underwent resection of large HCC.MethodsClinical data of 100 large HCC patients who underwent liver resection were retrospectively reviewed. All of them underwent protocol transarterial chemoinfusion (TACI) at 1 month.ResultsMedian tumor diameter was 13.8 cm, and 94% were single lesions. Systematic and non-systematic resections were performed in 91% and 9%, respectively, with R0 resection achieved in 84%. Overall 1-, 3- and 5-year survival rates were 76%, 38.5%, and 30.4%, respectively. Univariate analyses on patient survival revealed that intrahepatic metastasis on 1-month protocol TACI was the only significant risk factor (p=0.002). Mean ALP values according to the intrahepatic metastasis on 1-month protocol TACI were 124.6±76.9 IU/L and 145.1±92.6 IU/L, which did not show a statistical difference (p=0.23).ConclusionsIn patients with large HCC, 1-month protocol TACI combined with hepatic resection may contribute to the early detection and timely treatment of potentially preexisting metastatic lesions.

Ascites in patients with hepatocellular carcinoma: prevalence, associated factors, prognostic impact, and staging strategy.

Ascites may develop in patients with hepatocellular carcinoma (HCC) with coexisting liver cirrhosis. Few studies had specifically evaluated the role of ascites in HCC. This study investigated its prevalence, associated factors, prognostic impact, and staging strategy in a large HCC patient cohort. A total of 2,203 HCC patients were analyzed. The grading of ascites was according to the European Association for the Study of Liver. The prognostic ability of the Cancer of the liver Italian Program (CLIP), Barcelona Clinic Liver Cancer, Japan Integrated Scoring system, and Taipei Integrated Scoring system in HCC patients with ascites was compared using the Akaike information criterion (AIC). Ascites was present in 498 (23%) patients at diagnosis. Grades 1, 2, and 3 ascites were found in 13, 5, and 5% of the patients, respectively. The severity of ascites significantly correlated with hyperbilirubinemia, hypoalbuminemia, hyponatremia, prothrombin time (PT) prolongation, and renal insufficiency (all p<0.001). Large tumor burden and more frequent vascular invasion were often observed in patients with more severe ascites (both p<0.001). In the Cox proportional hazard model, ascites was identified as an independent prognostic predictor with 80-94% increased risk of mortality (p<0.001). Among HCC patients with ascites, the CLIP system had the lowest AIC value. Ascites is often seen in HCC patients and is associated with both tumoral and cirrhosis factors and decreased long-term survival. The CLIP staging system is a more feasible prognostic model for HCC patients with ascites. The optimal treatment strategy for these patients remains to be investigated.